[Research on indicators of ideological and political resource database construction for curriculum of "Epidemiology"].

Objective: To construct indicators of the ideological and political resource database construction for the curriculum of "Epidemiology". Methods: Two rounds of expert consultation were conducted in 15 experts from 4 universities and 1 textbook publishing house using the Delphi method, and the importance and feasibility scores of the indicators were calculated with the degree of concentration and coordination of experts' opinions. Results: In the two rounds of consultation, the experts' positive coefficient of the two questionnaires were both 100.00% (15/15), the authoritative coefficients of experts were both 0.83, and the Kendall's W was 0.27 (P<0.05) and 0.33 (P<0.05), respectively. Consensus was reached on 4 primary indicators and 31 secondary indicators. Conclusion: The process of this study is scientific, and the indicators for the construction of ideological and political resource database for the curriculum of "Epidemiology" are authoritative, which can promote the establishment of ideological and political resource database for the curriculum of "Epidemiology".

[Genotype-environment interaction on arterial stiffness: A pedigree-based study].

OBJECTIVE: To utilized the baseline data of the Beijing Fangshan Family Cohort Study, and to estimate whether the association between a healthy lifestyle and arterial stiffness might be modified by genetic effects. METHODS: Probands and their relatives from 9 rural areas in Fangshan district, Beijing were included in this study. We developed a healthy lifestyle score based on five lifestyle behaviors: smoking, alcohol consumption, body mass index (BMI), dietary pattern, and physical activity. The measurements of arterial stiffness were brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). A variance component model was used to determine the heritability of arterial stiffness. Genotype-environment interaction effects were performed by the maximum likelihood methods. Subsequently, 45 candidate single nucleotide polymorphisms (SNPs) located in the glycolipid metabolism pathway were selected, and generalized estimated equations were used to assess the gene-environment interaction effects between particular genetic loci and healthy lifestyles. RESULTS: A total of 6 302 study subjects across 3 225 pedigrees were enrolled in this study, with a mean age of 56.9 years and 45.1% male. Heritability of baPWV and ABI was 0.360 (95%CI: 0.302-0.418) and 0.243 (95%CI: 0.175-0.311), respectively. Significant genotype-healthy diet interaction on baPWV and genotype-BMI interaction on ABI were observed. Following the findings of genotype-environment interaction analysis, we further identified two SNPs located in ADAMTS9-AS2 and CDH13 might modify the association between healthy dietary pattern and arterial stiffness, indicating that adherence to a healthy dietary pattern might attenuate the genetic risk on arterial stiffness. Three SNPs in CDKAL1, ATP8B2 and SLC30A8 were shown to interact with BMI, implying that maintaining BMI within a healthy range might decrease the genetic risk of arterial stiffness. CONCLUSION: The current study discovered that genotype-healthy dietary pattern and genotype-BMI interactions might affect the risk of arterial stiffness. Furthermore, we identified five genetic loci that might modify the relationship between healthy dietary pattern and BMI with arterial stiffness. Our findings suggested that a healthy lifestyle may reduce the genetic risk of arterial stiffness. This study has laid the groundwork for future research exploring mechanisms of arterial stiffness.

[Metformin use and risk of ischemic stroke in patients with type 2 diabetes: A cohort study].

OBJECTIVE: To explore the association between the use of metformin and the risk of ischemic stroke in patients with type 2 diabetes. METHODS: A prospective cohort study was designed from the Fangshan family cohort in Beijing. According to metformin use at baseline, 2 625 patients with type 2 diabetes in Fangshan, Beijing were divided into metformin group or non-metformin group and the incidence of ischemic stroke between the different groups during follow-up was estimated and compared by Cox proportional hazard regression model. The participants with metformin were first compared with all the parti-cipants who did not use metformin, and then were further compared with those who did not use hypoglycemic agents and those who used other hypoglycemic agents. RESULTS: The patients with type 2 diabetes were with an average age of (59.5±8.7) years, and 41.9% of them were male. The median follow-up time was 4.5 years. A total of 84 patients developed ischemic stroke during follow-up, with a crude incidence of 6.4 (95%CI: 5.0-7.7) per 1 000 person-years. Among all the participants, 1 149 (43.8%) took metformin, 1 476 (56.2%) were metformin non-users, including 593 (22.6%) used other hypoglycemic agents, and 883 (33.6%) did not use any hypoglycemic agents. Compared with metformin non-users, the Hazard ratio (HR) for ischemic stroke in metformin users was 0.58 (95%CI: 0.36-0.93; P = 0.024). Compared with other hypoglycemic agents, HR was 0.48 (95%CI: 0.28-0.84; P < 0.01); Compared with the group without hypoglycemic agents, HR was 0.65 (95%CI: 0.37-1.13; P=0.13). The association between metformin and ischemic stroke was statistically significant in the patients ≥ 60 years old compared with all the metformin non-users and those who used other hypoglycemic agents (HR: 0.48, 95%CI: 0.25-0.92; P < 0.05). Metformin use was associated with a lower incidence of ischemic stroke in the patients with good glycemic control (0.32, 95%CI: 0.13-0.77; P < 0.05). In the patients with poor glycemic control, and the association was not statistically significant (HR: 0.97, 95%CI: 0.53-1.79; P>0.05). There was an interaction between glycemic control and metformin use on incidence of ischemic stroke (Pinteraction < 0.05). The results of the sensitivity analysis were consistent with the results in the main analysis. CONCLUSION: Among patients with type 2 diabetic in rural areas of northern China, metformin use was associated with lower incidence of ischemic stroke, especially in patients older than 60 years. There was an interaction between glycemic control and metformin use in the incidence of ischemic stroke.

[Family-based association tests for rare variants].

Next-generation sequencing has revolutionized family-based association tests for rare variants. As the lower power of genome wide association study for detecting casual rare variants, methods aggregating effects of multiple variants have been proposed, such as burden tests and variance component tests. This paper summarizes the methods of rare variants association test that can be applied for family data, introduces their principles, characteristics and applicable conditions and discusses the shortcomings and the improvement of the present methods.

[Exploring the association between de novo mutations and non-syndromic cleft lip with or without palate based on whole exome sequencing of case-parent trios].

OBJECTIVE: To explore the association between de novo mutations (DNM) and non-syndromic cleft lip with or without palate (NSCL/P) using case-parent trio design. METHODS: Whole-exome sequencing was conducted for twenty-two NSCL/P trios and Genome Analysis ToolKit (GATK) was used to identify DNM by comparing the alleles of the cases and their parents. Information of predictable functions was annotated to the locus with SnpEff. Enrichment analysis for DNM was conducted to test the difference between the actual number and the expected number of DNM, and to explore whether there were genes with more DNM than expected. NSCL/P-related genes indicated by previous studies with solid evidence were selected by literature reviewing. Protein-protein interactions analysis was conducted among the genes with protein-altering DNM and NSCL/P-related genes. R package "denovolyzeR" was used for the enrichment analysis (Bonferroni correction: P=0.05/n, n is the number of genes in the whole genome range). Protein-protein interactions among genes with DNM and genes with solid evidence on the risk factors of NSCL/P were predicted depending on the information provided by STRING database. RESULTS: A total of 339 908 SNPs were qualified for the subsequent analysis after quality control. The number of high confident DNM identified by GATK was 345. Among those DNM, forty-four DNM were missense mutations, one DNM was nonsense mutation, two DNM were splicing site mutations, twenty DNM were synonymous mutations and others were located in intron or intergenic regions. The results of enrichment analysis showed that the number of protein-altering DNM on the exome regions was larger than expected (P < 0.05), and five genes (KRTCAP2, HMCN2, ANKRD36C, ADGRL2 and DIPK2A) had more DNM than expected (P < 0.05/(2×19 618)). Protein-protein interaction analysis was conducted among forty-six genes with protein-altering DNM and thirteen genes associated with NSCL/P selected by literature reviewing. Six pairs of interactions occurred between the genes with DNM and known NSCL/P-related genes. The score measuring the confidence level of the predicted interaction between RGPD4 and SUMO1 was 0.868, which was higher than the scores for other pairs of genes. CONCLUSION: Our study provided novel insights into the development of NSCL/P and demonstrated that functional analyses of genes carrying DNM were warranted to understand the genetic architecture of complex diseases.

[Incidence and risk factors of ischemic stroke in patients with type 2 diabetes among urban workers in Beijing, China].

OBJECTIVE: To explore the incidence of ischemic stroke after the onset of type 2 diabetes, and further analyze the risk factors, so as to provide a basis for further research. METHODS: The data were obtained from the database of the Beijing Urban Employee Basic Medical Insurance Database. The study used a prospective design to describe the incidence of ischemic stroke in patients with type 2 diabetes. In our study, these patients were followed up for seven years. Multivariate Logistic regression models were used to analyze the risk factors of ischemic stroke in patients with type 2 diabetes. RESULTS: A total of 185 813 newly diagnosed type 2 diabetes patients were enrolled, with an average age of (58.5±13.2) years, and 49.0% of them were males. A total of 10 393 patients with newly diagnosed ischemic stroke occurred in 7 years, with a cumulative incidence of 5.6% and an incidence density of 8.1/1 000 person-years. Ischemic stroke occurred in all age groups in patients with type 2 diabetes. The cumulative incidence was 1.5% (95%CI: 1.3%-1.6%) in group ≤44 years old, 3.6% (95%CI: 3.4%-3.7%) in group 45-54 years old, 5.4% (95%CI: 5.2%-5.5%) in group 55-64 years old, and 9.2% (95%CI: 9.0%-9.4%) in group ≥65 years old, and the cumulative incidence increased with age (P < 0.05). Cumulative incidence rate of the males (6.8%, 95%CI: 6.7%-7.0%) was higher than the females (4.4%, 95%CI: 4.3%-4.6%). Among the patients < 80 years old, the cumulative incidence rate of the males was higher than that of the females in all the age groups. In the patients ≥80 years of age, the cumulative incidence was higher in the females (9.2%) than in the males (7.9%). Further analysis revealed that complications, such as coronary heart disease (OR=3.18, 95%CI: 2.72-3.72), heart failure (OR=1.53, 95%CI: 1.32-1.79) and kidney failure (OR=1.45, 95%CI: 1.20-1.75) were associated with ischemic stroke in the patients with type 2 diabetes. CONCLUSION: The incidence level of ischemic stroke in patients with type 2 diabetes is high. It is necessary to strengthen the management of risk factors in elderly patients, screen the complications of type 2 diabetes as early as possible, and take active preventive and control measures.

[Venous thromboembolism risk and prophylaxis status of cancer inpatient].

Objective: To determine the risk profile of venous thromboembolism (VTE) and evaluate VTE prophylaxis implementation of the hospitalized cancer patients in the DissolVE 2 study. Methods: The data of hospitalized cancer patients in the DissolVE 2 study were analyzed. The risk distribution of VTE, preventive measures and in-hospital VTE events of hospitalized patients with tumors were described by percentage and 95% confident interval (CI). Results: A total of 1 535 cancer patients were included. According to the Padua score, 826 (53.8%) patients were at low risk of VTE, while 709 (46.2%) patients were at high VTE risk. VTE events occurred in 4 low-risk patients (0.5%; 95%CI: 0.1%, 1.2%) and 5 high-risk patients (0.7%; 95%CI: 0.2%, 1.6%). The overall incidence was 0.6% (9/1 535, 95%CI: 0.3%, 1.1%). Among patients with high VTE risk, 666 (93.9%) did not receive any VTE prophylaxis, and only 11 (1.6%) patients received appropriate VTE prophylaxis. Among patients who received VTE prevention, no VTE event was observed. Conclusions: Nearly half of the hospitalized cancer patients are at high risk of VTE, but most of them don't receive VTE prophylaxis. The results reflect the insufficient management of VTE risk for hospitalized cancer patients in China, and improvement of awareness and practice of VTE prophylaxis is urgently needed.

[Research progression in clinical treatment of gastric cancer in 2020].

Gastric cancer is a common type of malignant tumors, but its clinical prognosis remains unsatisfactory. Up to 2020, a growing number of high-quality clinical researches has provided reliable evidence for clinical practice. Evidences from surgery, perioperative treatment and immunotherapy, such as changes in surgical methods, improvement of perioperative chemotherapy and combination of immune and chemotherapy strategy, provided the possibility to improve the clinical efficacy of gastric cancer. In our clinical practice, gastrointestinal surgeons need to integrate the current research progression and develop individualized strategy for different patients, which is expected to further improve the prognosis and quality of life for patients with gastric cancer.

[Clinicopathological features and prognosis of 59 patients with platelet-derived growth factor α-mutant gastrointestinal stromal tumor].

Objective: Platelet-derived growth factor α (PDGFRA)-mutant gastrointestinal stromal tumor (GIST) is a relatively rare disease, whose clinicopathological characteristics and prognosis have been poorly studied. In this paper, the clinicopathological features and prognostic factors of PDGFRA-mutant GIST are investigated to provide more data for its understanding and treatment. Methods: A retrospective case-control study was used to collect the medical records of patients with GIST who underwent surgical resection in Zhongshan Hospital of Fudan University from January 2015 to August 2019. Patients with PDGFRA-mutant GIST were enrolled, and those with synonymous PDGFRA mutations, non-tumor-related deaths, and lack of clinicopathological data were excluded. The clinicopathological data were collected and the risk factors associated with prognosis were analyzed. Results: Among the enrolled 59 patients, there were 41 males (69.5%) and 18 females (30.5%) with the median age of 60 (25-79) years. All tumors originated from the stomach. The tumor size was 5 (3-7) cm, and the mitotic count was 2 (1-4)/50 high-power fields (HPF). According to the modified NIH risk stratification, 8 cases were classified as very low risk (13.6%), 25 cases as low risk (42.4%), 14 cases as moderate risk (23.7%), and 12 cases as high risk (20.3%). There were 7 cases of exon 12 mutation and 52 cases of exon 18 mutation (including 36 cases of D842V mutation). A comparison of clinicopathological features between the D842V mutation group and the non-D842V mutation group showed no statistically significant difference (all P>0.05). During a median follow-up of 21 (0-59) months, the 1- and 3-year relapse-free survival (RFS) rates of all the patients were 96.6% and 91.5%, respectively. There were 8 cases of recurrence and 3 cases of death. Six GIST patients with D842V mutation had tumor recurrence after operation, of whom 4 cases achieved varying degrees of tumor remission after being treated with dasatinib or avapritinib. Log-rank analysis showed that the overall survival (OS) of male was better than that of female (100% vs. 83.3%, P=0.046), but there was no significant difference in OS among patients with different risk grades (P=0.057). The RFS and OS of patients with D842V mutation and non-D842V mutation, exon 12 and exon 18 mutation were similar (all P>0.05). Univariate Cox analysis showed that RFS was associated with gender (P=0.010), tumor size (P=0.042), mitotic count (P=0.003), and the modified NIH risk stratification (P=0.042), while multivariate analysis revealed that higher risk grade was an independent risk factor for recurrence of PDGFRA-mutant GIST (HR=12.796, 95%CI: 1.326-123.501, P=0.028). Gender was an independent factor for recurrence, and the risk of recurrence in males was lower than that in females (HR=0.154, 95%CI: 0.028-0.841, P=0.031). Conclusions: Gender and the modified NIH risk stratification are independent risk factors for recurrence of PDGFRA-mutant GIST, while patients with D842V and non-D842V mutation, and exon 12 and exon 18 mutation have a similar risk of recurrence and death.

Clinical outcomes of different therapeutic modalities for rectal gastrointestinal stromal tumor: Summary of 14-year clinical experience in a single center.

OBJECTIVE: The optimal treatment for gastrointestinal stromal tumor (GIST) of the rectum is controversial due to the extremely low incidence of the disease. The aim of the present study was to compare the clinical outcomes of different treatment modalities for rectal GIST by reviewing the 14-year experience in our center. METHOD: Medical records of rectal GIST patients who received surgical treatment in our center between January 2004 to December 2017 were reviewed retrospectively. Overall survival (OS) and recurrence-free survival (RFS) were used as the observation endpoints. RESULTS: Included in this study were 71 GIST patients, including 42 patients who underwent local excision (LE) and 29 patients who underwent segmental resection (SR). There were differences in tumor size (P = 0.001) and malignant risk grade (P = 0.007). The LE approach achieved a lower rate of R0 resection than SR (29/42 vs.27/29, P = 0.015) and shorter hospital stay (P = 0.004). Preoperative imatinib mesylate (IM) therapy improved the rate of sphincter-sparing surgery for patients with tumors in the very low segment of the rectum (P = 0.012) and offered better R0 resection margins (P = 0.027). Multivariate analysis showed that the resection margin status (P = 0.014), risk stratification (P = 0.001) and IM therapy (P = 0.042) were independent factors affecting RFS of rectal GIST patients but not the surgical modalities (LE vs. SR, P = 0.802). Multivariate analysis showed no significant impact of these variables on OS. CONCLUSION: Selection of surgical modalities has no significant impact on the prognosis. Local excision is the preferred surgical modality for resectable rectal GIST by virtue of less injury and shorter hospital stay. IM therapy has proved to be associated with improved RFS for rectal GIST patients.

[The shift of the treatment strategy of gastrointestinal stromal tumor from the surgical perspective].

As tumors originated from mesenchymal tissue, gastrointestinal stromal tumors (GIST) has its own typical history. For the idea of treatment for GIST at different historical periods, the role and value of surgery for the treatment of GIST keep changing. Laparoscopy and endoscopy will have the role they deserved. With the understanding of pathogenesis of GIST, targeted chemotherapy will be more and more accurate and individualized. How to improve the overall therapeutic effect of GIST, especially for the patients with the high risk and drug-resistance, is the dilemma and challenges for the surgeons.

[Retrospect of 2019: focus on the research progress of gastric neoplasm].

Gastric carcinoma, gastrointestinal stromal tumor and gastric neuroendocrine tumor are the most common gastric neoplasms. A series of researches in 2019 showed that the safety and efficacy of laparoscopic gastrectomy in the treatment of both early and advanced gastric cancer patients are similar to open surgeries, providing a high-level evidence-based medical basis for the promotion of laparoscopic surgery in the treatment for gastric cancer. In multidisciplinary treatment and perioperative chemoradiotherapy, major research results have also been published, and clinical researches in China are gradually gaining international recognition and attention. Although the application of targeted therapy and immunotherapy has made progress, the first-line therapy after gastric cancer surgery has not been established. In the field of gastrointestinal stromal tumors, laparoscopic surgery has gradually been recognized, and surgical treatment of patients with advanced drug resistance still has its value. In terms of gastric neuroendocrine tumors, the latest researches showed that surgical methods should be selected according to tumor characteristics, and gastric adenocarcinoma with neuroendocrine components may have a worse prognosis.

Ultralow Thermal Conductivity and Extraordinary Thermoelectric Performance Realized in Codoped Cu3SbSe4 by Plasma Spark Sintering.

Cu3SbSe4-based materials have attracted much attention for thermoelectric power generation in the mid-temperature range due to their low cost, ecofriendliness, and abundant elements on the earth. However, the peak figure of merit (ZT) for the Cu3SbSe4-based system prepared by the fusion method is usually smaller than unity because of its high thermal conductivity. Here, we show that through a coprecipitation method combined with spark plasma sintering ultrafine-grained Cu3Sb0.94Sn0.06Se4-ySy (y = 0, 0.5) embedded with Cu3SbSe3 nanoprecipitates can be prepared. Due to the ultralow thermal conductivity and enhanced Seebeck coefficient, a record-high ZT value of 1.32 is achieved for the sample Cu3Sb0.94Sn0.06Se3.5Se0.5. The ultralow thermal conductivity is attributed to the enhanced phonon scattering caused by the nanoprecipitates and fine grains of the samples, and the improved Seebeck coefficient originates from the enhancement of electronic density-of-state effective mass. Present results demonstrate that excellent thermoelectric performance can be realized in dual-substituted and fine-grained Cu3Sb0.94Sn0.06Se4-ySy with nanoprecipitates.

[Analysis of the contradiction between the supply and demand of Chinese graduate students' emergency professional ability in public health and preventive medicine in China].

In order to underst and the status of health emergency personnel training development and raising coping measures, electronic questionnaire surveys were conducted among 22 colleges and universities in different region of China. The result showed that colleges universities in China invested less in the training of emergency personnel. It is different and emphasized particularly for the cultivation of emergency professional ability among different types of public health students. Universities and employer hold relative evaluation of students' emergency professional ability with distinct regional differences.

[Study on the current status of postgraduates training in public health and preventive medicine in China in 2016].

To investigate the current status of postgraduates training in public health and preventive medicine in China. In this study, a questionnaire survey was conducted among directors of enrollment and teaching in 22 universities with postgraduate admission qualifications in corresponding disciplines nationwide. In 2016, full-time postgraduates were mainly academic masters. In addition to the graduate entrance examination, the common enrollment mode in colleges was to enroll a high qualified student with recommendations from relevant experts or institutions and an exemption from entrance examination (20/22). The emphasis on training contents between academic and public health master was different. Currently, the scale of public health postgraduate enrollment in public health and preventive medicine in China is stable, and the training program is reasonable, but there is an issue of monotonous model and uneven distribution of enrollment.

[Investigation on the current status of the cultivation of the master of public health (MPH) in colleges in China].

In order to understand the status of the cultivation of the masters of public health (MPH) in colleges in China and improve the cultivation model, an electronic questionnaire survey were conducted among 22 schools of public health in colleges. The result showed that the size and the enrolment scale of Chinese MPH students were relatively small, and the training objectives were still unclear. There was no obvious difference between the curriculum setting for MPH and academic master degree. The practical skill-oriented courses and emergency response ability of public health practice were insufficient. The cultivation model of MPH should be improved in future.

[Construction of 3ß-HSD gene silencing cell line and its effects on apoptosis induced by DEHP].

Objective: To construct 3ß-HSD gene shRNA lentivirus interference vecto, then transfect into human MCF-7 cells, and construct cell line with 3ß-HSD gene silencing, finally to study the effects of 3ß-HSD on apoptosis induced by di- (2-ethylhexyl) phthalate (DEHP) . Methods: According to the mRNA sequence of 3ß-HSD gene provided by GenBank, three interference sequences were designed and connected to PLVX-shRNA2-puro after annealing. The recombinant lentivirus vector was transfected into 293FT cells, the virus supernatants were collected and infected with MCF-7 cells. After puromycin screening, MCF-7 cells with 3ß-HSD gene silencing were constructed. The cells with 3ß-HSD gene silencing were identified by real-time quantitative PCR and western blot. Then the 3ß-HSD gene silencing cells and MCF-7 cells were treated at various doses of DEHP for 24 hours to detect the gene expression and protein expression of apoptosis genes including Bax, Caspase-3 and Caspase-8. Results: The interference sequence of 3ß-HSD gene inserted into lentivirus vector PLVX-shRNA2-puro is consistent with the designed sequence. 3ß-HSD gene expression level in MCF-7 cells with 3ß-HSD gene silencing was 77% lower than than that of control MCF-7 cells. 3ß-HSD protein level in MCF-7 cells with 3ß-HSD gene silencing was 74% lower than that of control MCF-7 cells. After DEHP treatment in MCF-7 cells with 3ß-HSD gene silencing and control MCF-7 cells, qRT-PCR results showed that Bax gene expression levels increased by 28%-54%, Caspase-3 gene increased by 13%-49%, Caspase-8 gene increased by 21%-70% in MCF-7 cells when compared with the control group. Additionally, in the 3ß-HSD gene silencing cells, Bax gene expression level decreased by 11%-28%, Caspase-3 gene expression decreased by 12%-23%, Caspase-8 gene expression decreased by 11%-34%, compared with the same treatment group of MCF-7 cells. Western blot results showed that Bax protein expression level increased by 28%-61%, Caspase-3 protein expression level increased by 40%-48%, Caspase-8 protein increased by 31%-84% in MCF-7 cells when compared with the control group. In 3ß-HSD gene silencing cells, Bax protein expression level increased by 11%-27%, Caspase-3 protein increased by 21%-40%, Caspase-8 protein increased by 12%-25%, compared with the same treatment group of MCF-7 cells. Conclusion: The stable 3ß-HSD gene silencing cell line are successfully constructed in this study. DEHP can induce increased expression of apoptotic gene and protein. Silencing of 3ß-HSD gene can inhibit the activation of apoptotic gene by DEHP in a certain degree.

[Preparation and evaluation of blank and doxorubicin loaded poly (acrylic acid) microspheres for embolization].

OBJECTIVE: To prepare ion exchange doxorubicin-loaded poly (acrylic acid) microspheres (DPMs) and evaluate the properties of these chemoembolic agents. METHODS: Poly (acrylic acid) microspheres (PMs) without drug were prepared by inverse suspension polymerization method and then doxorubicin was loaded by ion exchange mechanism to prepare DPMs. Optical microscope was used to investigate the morphology and particle size distribution of PMs and DPMs; fluorescence microscope and confocal microscope were used to observe the distribution of doxorubicin after drug loading. Elasticities of both the microspheres were evaluated by texture analyzer. High performance liquid chromatography (HPLC) method was established to determine the drug loading behavior of PMs and releasing behavior of DPMs. The in vivo embolic property was evaluated by embolizing the hepatic artery of a rabbit with 0.1 mL of DPMs. RESULTS: PMs and DPMs were both spherical in shape, smooth in surface and dispersed well. Doxorubicin was mainly in the outer area inside of DPMs and distributed evenly. The average particle size of PMs and DPMs were (283±136) µm and (248±149) µm, respectively. PMs and DPMs both had good compression ability with the Young's modulus of (62.63±1.65) kPa and (93.94±1.10) kPa separately. PMs reached the drug loading balance at 12 h, and the entrapment efficiency was greater than 99%. Drug loading of PMs in doxorubicin solution at the concentration of 5.0 g/L and 12.5 g/L was (19.78±0.27) g/L and (49.45±0.37) g/L, respectively. Doxorubicin released slowly from DPMs in PBS and the accumulative release percentages of DPMs with corresponding drug loading were 6.82%±0.02% and 2.83%±0.10% after 24 h, respectively. Arterial angiograms showed that the hepatic artery of the rabbit was successfully embolized with DPMs. CONCLUSION: DPMs with good performance of loading doxorubicin could be a potential embolic agent for transcatheter arterial chemoembolization.

[KRAS mutations analysis in mucinous epithelial lesions of the endometrium].

Objective: To investigate the frequency of KRAS mutation in mucinous epithelial lesions of the endometrium, and analyze the correlation between KRAS mutation and the clinicopathologic features. Methods: The cohort included forty-three cases of mucinous epithelial lesions of the endometrium selected from July 2015 to October 2017 from Beijing Obstetrics and Gynecology Hospital, and 22 control cases. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue sections. Polymerase chain reaction amplification for KRAS exons 2 and 3 was performed, followed by sequencing using capillary electrophoresis. The Fisher exact test was used to compare the prevalence of KRAS mutation among the different groups. Results: The patients'age ranged from 33 to 77 years [mean (55.12±9.34) years, median 55 years]. None of the eight cases of endometrial hyperplasia with mucinous differentiation without atypia showed KRAS mutation. The frequency of KRAS mutations was 1/10 in endometrial atypical hyperplasia, 1/12 in endometrioid carcinoma, 4/11 in endometrial atypical hyperplasia with mucinous differentiation (EAHMD), 6/15 in endometrioid carcinoma with mucinous differentiation (ECMD) and 8/9 in mucinous carcinoma (MC), respectively. The differences were statistically significant between MC versus EC (P<0.01) and MC versus ECMD (P<0.05). Conclusion: The high frequency of KRAS mutation in EAHMD, ECMD and MC indicates that KRAS mutational activation is implicated in the pathogenesis of endometrial mucinous carcinoma.